Vinylogous amide analogues of diaminopimelic acid (DAP) as inhibitors of enzymes involved in bacterial lysine biosynthesis

被引：25

作者：

Caplan, JF

Zheng, RJ

Blanchard, JS

Vederas, JC ^{[1
]}

机构：

[1] Univ Alberta, Dept Chem, Edmonton, AB T6G 2G2, Canada

[2] Yeshiva Univ Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA

来源：

ORGANIC LETTERS | 2000年 / 2卷 / 24期

关键词：

D O I：

10.1021/ol000271e

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

[GRAPHICS] Vinylogous amides 5 and 6 have been synthesized from L-propargyl glycine and tested against diaminopimelate (DAP) enzymes involved in bacterial lysine biosynthesis, Both are reversible inhibitors of DAP D-dehydrogenase and DAP epimerase with IC50 values in the 500 muM range, Compound 5 shows competitive inhibition against the L-dihydrodipicolinate (DHDP) reductase with a K-i value of 32 muM, which is comparable to the planar dipicolinate 16 (K-i = 26 muM), the best known inhibitor of the enzyme.

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页码：3857 / 3860

页数：4

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